Abstract

In this work, the tumor-targeted ultra-pH-responsive conjugates (PBA/Dex-g-OE) and nontargeted conjugates (Dex-g-OE) were successfully prepared and could easily self-assemble into stable micelles with lower CMC values in neutral aqueous solution. Transmission electron microscopy and dynamic light scattering measurement indicated that the resulting micelles have desirable size distribution and regular spherical shape. The PBA/Dex-g-OE micelles possessed high stability in physiological condition and were pH sensitive to both extracellular and intracellular acidic conditions. Doxorubicin (DOX) was efficiently loaded to give the DOX-loaded micelles (PBA/Dex-g-OE-DOX and Dex-g-OE-DOX) with the desirable drug loading contents. In vitro cellular uptake and growth inhibition assays suggested that PBA/Dex-g-OE-DOX micelles were more efficiently internalized by monolayer tumor cells and three-dimensional multicellular tumor spheroids (MCTS) than nontargeted micelles (Dex-g-OE-DOX), leading to the fast and complete destruction of MCTS in vitro.

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Acknowledgements

This work is financially supported by the National Natural Science Foundation of China (Nos. 21174054, 21004030, and 51503001), the Natural Science Foundation of Anhui Province of China (No. 1408085MB26), and the Doctor Research Foundation of Anhui University of China (No. J10113190075), and the Academic and Technology Introduction Project of Anhui University of China (AU02303203), and the Nature Science Research Programme of the Education Office of Anhui Province (Nos. KJ2016A030 and KJ2018ZD003).